This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Center for Psychiatric Neuroscience (CPN) examines the neurochemical causes of depression. Of all mental illnesses, depression is the most common disorder and is a serious and persistent medical illness affecting the thoughts, mood, activity, and physical health of 9.9 million American adults in any given year. Integrated studies conducted by CPN investigators use postmortem brain tissue from animals treated chronically with an antidepressant drug or exposed to chronic stress to examine novel hypotheses that may ultimately lead to more effective treatments for this debilitating disease. The CPN and the University of Mississippi Medical Center (UMC) use research animals when the information that will be gained may be useful in saving human lives or treating disease and/or when the information cannot be gained without the use of animals. The CPN and UMC recognize its ethical responsibility to treat animals involved in research humanely, and require that all faculty and staff involved in animal research undergo vigorous training and maintain the highest standards of care. The CPN Animal Core provides brain tissue from animal subjects that have been treated either pharmacologically or behaviorally in a manner that allows CPN investigators to address the specific aims of their individual projects. To allow the assessment of the effects of long-term antidepressant exposure on central nervous system parameters, animals are treated long-term with fluoxetine and sacrificed for postmortem studies of changes in the brain. In addition to the studies with fluoxetine, other animals are exposed to a chronic stress paradigm that results in behavioral symptoms that may be related to human depression. Chronic restraint stress results in alterations in some features of the glutamate and serotonin systems that may well be relevant to the changes detected in these systems in human depression. William L. Woolverton, Ph.D., provides overall supervision of the Animal Core. He is a behavioral pharmacologist with 30 years experience with pharmacological research in behavioral and neurochemical studies. Javier Miguel-Hidalgo, Ph.D., supervises brain dissection, collection and storage. Dr. Miguel-Hidalgo is a neuroanatomist with 18 years experience in dissection, freezing, fixation, storage, and histochemical processing of brain samples in a variety of vertebrate species. Patrick Kyle, Ph.D., will assess fluoxetine levels in blood samples. Dr. Kyle is an analytical toxicologist with 14 years experience in drug analysis and analytical methods development involving GC/MS, HPLC, and LC/MS.